Studies have continued to determine the molecular and cellular targets of estrogenic chemicals and establish the mechanisms by which interactions of estrogens with developing genital tract target cells result in permanently altered differentiation, including dysmorphology and neoplasia. In the developmentally-estrogenized mouse, neoplasias in the female structures derived from the Mullerian duct (e.g., uterus) were demonstrated to be hormonally dependent, transplantable tumors; cell lines established from them were shown to progressively lose the estrogen receptor (ER) as well as hormone-dependent growth. The chronological expression of oncogenes and tumor suppressor genes is also being studied. The developing Mullerian duct has been further studied at the cellular and molecular levels. It was determined that in the immature mouse uterus, the epithelium was relatively deficient in detectable ER although the mitogenic signal of estrogen is apparently transduced in ER deficient epithelial cells. The presence of epidermal growth factor receptor (EGFR) in these cells suggests that the mitogenic signal of estrogens early in development may involve growth factors such as EGF. This is further supported by experiments in immature mice in which EGF can replace estrogen in stimulating uterine and vaginal growth and differentiation. Studies on phospholipid turnover (especially phosphoinositides) may provide further insights into signal transduction mechanisms associated with estrogens. The growth characteristics of murine uterine epithelium and stroma were compared in serum-free tissue culture. The relative role of tissue-specific factors versus blood-borne cellular factors was examined in the newborn mouse uterus using the enzyme peroxidase as a marker for eosinophilic responses. These studies together support a complex developmental progression in hormone responsiveness in the female genital tract with important clues for neoplasia.